Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis

Background Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes. Methods We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573). Results The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66–91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83–96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98–99%; I2 = 12.08%) and 97% (95% CI: 94–99%; I2 = 72.50%), respectively. Conclusions Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-023-03186-x.


Background
Group B streptococcus (GBS) is a commensal bacterium that is generally found in the gastrointestinal and genitourinary tracts of pregnant women [1] and can be passed to their baby via maternal rectovaginal colonisation during labour, causing neonatal early-onset GBS disease (EOGBS) [1,2].Maternal rectovaginal GBS colonisation varies between populations but is estimated to occur transiently in approximately 18% of pregnant women worldwide [3,4].GBS is a leading cause of adverse maternal and neonatal outcomes, including maternal and neonatal sepsis, stillbirth, and infant death [1].
Intrapartum antibiotic prophylaxis (IAP) can prevent EOGBS [5].The World Health Organization (WHO) recommends IAP administration to women with GBS colonisation, within the context of local policy and guidance on GBS screening [4].Some countries like the Netherlands and the United Kingdom recommend risk-based protocols, giving IAP only in the presence of peripartum clinical risk factors.Other countries, like the United States (US), recommend both risk-based and universal culture-based screening for GBS colonisation, so that IAP can be given in the case of known colonisation [5].Culture-based testing remains the standard for antepartum screening [2].There is currently no international consensus on whether to recommend risk-based or universal culture-based screening for GBS [5].The need for laboratory processing limits testing capabilities in low-resource settings [6].A 2020 systematic review and meta-analysis found that screening-based protocols were associated with a reduced risk of EOGBS compared to risk-based protocols, without an associated higher antibiotic administration rate [5].If pregnant women do screen for GBS colonisation, it is important that the sampling approach has reasonable test accuracy, as false positives can contribute to overtreatment and resultant risk of antibiotic resistance, as well as having adverse effects on neonatal microbiome development [5].Conversely, false negatives present a missed treatment opportunity to reduce the risk of maternal and infant morbidity and mortality [5].
GBS testing is most sensitive when performed near or at term [7].GBS detection rates are higher when a combined vaginal-rectal swab is taken compared to a single vaginal or rectal swab only [8].Testing is traditionally done with GBS culture, either by or direct plating and/ or incubating the specimen in enriched culture medium.Enriched culture has a higher sensitivity than direct plating alone [9].Nucleic acid amplification test (NAAT) methodology for GBS testing is available; however, it has limitations, such as the inability to perform susceptibility testing.NAAT has not yet been universally adopted [2].WHO defines self-care as, "the ability of individuals, families and communities to promote health, prevent disease, maintain health and cope with illness and disability with or without the support of a health worker… Self-care interventions are tools that support self-care." Self-care interventions include self-collection of samples [10]; this involves an individual taking their own specimen, which is sent to a laboratory for processing [11].Systematic reviews comparing self-collected and healthcare provider-collected samples in the general population have found comparable accuracy for reproductive tract infection (RTI) testing, including sexually transmitted infections (STIs) [12] and human papillomavirus (HPV) [13].A 2019 systematic review found that self-collection of samples for STI diagnosis in the general population offers convenience, confidentiality, expanded access, and increased patient autonomy and empowerment [11].Self-sampling for STIs is acceptable to patients [14], and programmes offering selfcollection have been found to increase uptake of STI testing [11,15,16] and case finding [11], without significant adverse outcomes [15].This may not necessarily translate into increased uptake of screening for GBS during pregnancy, as barriers specific to STI screening, like stigma, may not be as significant an issue for GBS sampling, which is a routine part of antenatal care in some countries.However, screening enablers such as increased acceptability of and reduced embarrassment associated with self-sampling compared to providercollection may be transferrable.
The US Centres for Disease Control and Prevention guidelines advise that, when paired with clear patient instructions, self-collected vaginal-rectal specimens in pregnancy have similar GBS culture yield rates to provider-collected specimens [2].However, the supporting evidence for this advice are studies that have not been formally synthesised [17][18][19][20].No previous systematic review has assessed the accuracy of self-collected samples for RTIs in pregnancy, including GBS, and whether self-collection of samples for RTIs in pregnancy can improve maternal and perinatal health outcomes.
Ensuring there is high quality evidence that sample self-collection for GBS screening is as accurate as provider-sampling presents an opportunity for a strengthened evidence base to support self-care interventions during pregnancy.Expansion of self-care in this context could improve patient choice, convenience, and autonomy, as well as expand antenatal care coverage, ultimately improving health outcomes [21].This review aimed to determine (1) whether self-collected samples are as sensitive and specific as provider-collected samples for detection of GBS colonisation in pregnant individuals and (2) whether a self-collection strategy for detection of GBS in pregnancy compared to provider-collection can improve maternal and perinatal health outcomes.

Search strategy and assessment of eligibility
This systematic review and meta-analysis is part of a larger systematic review (PROSPERO CRD42023396573) which aims to determine the diagnostic accuracy and health effects of sample self-collection for RTI testing in pregnant individuals, compared to provider-collection.In this paper, we report on studies assessing GBS colonisation (results for other RTIs will be reported separately).We report these findings according to PRISMA-DTA guidelines (see Additional file 1 for PRISMA Checklist) [22].
Eligible studies included those comparing self-collected to provider-collected samples for GBS testing of pregnant individuals.We included studies whose population were entirely or partially comprised of pregnant individuals, provided that disaggregated data for pregnant participants could be obtained (either from the published article, or by contacting study investigators).Studies were eligible if self-collected and provider-collected samples were taken from the same participant or participants were randomised to either self-collection or provider-collection.To be eligible, studies needed to have all participant samples collected from the same anatomical site, with the same type of sampling device, following the same sample transport process, with the same sample processing and test performed on both samples, using the same test cut off.Eligible studies were those reporting positive and negative test results for both self-collected and provider-collected samples.Randomised or quasi-randomised controlled trials, controlled before-after studies, interrupted-time-series studies, historically controlled studies, cohort studies, cross-sectional studies and case-control studies were eligible.We excluded case reports, case series, conference abstracts, poster presentations, editorials, correspondence, and qualitative studies.For protocols of ongoing trials dated 2019 or later, we contacted authors to see if trial data were available.
The following databases were searched on 18-21 June 2022: CINAHL Plus via EBSCOhost (from 1937), Medline and EMBASE (from 1946), Maternity and Infant Care Database (from 1971), Cochrane Central Register of Controlled Trials (from 1998), and the Cochrane Database of Systematic Reviews (from 1996) via Ovid.The search strategy combined keywords and subject headings on self-care (including self-sampling and self-collection) AND pregnancy AND reproductive tract infections (see Additional file 2 for full search strategy).No date or language restrictions were applied.We conducted a manual search of the reference lists of systematic reviews on similar topics for non-pregnant participants, as well as those of included studies in this review.
Two reviewers independently screened all titles/ abstracts and potentially eligible full texts for inclusion using Covidence, according to the eligibility criteria.Any disagreements were resolved through discussion or consulting a third reviewer.When warranted, Google Translate was used for studies not in English.For eligible randomised trials, two independent reviewers assessed trial integrity using an adapted research integrity assessment (RIA) checklist tool, which consists of six domains to assess trial research integrity [23,24].We reported findings from the RIA tool for each study by domain and contacted study authors for further information regarding these concerns.

Data extraction, quality assessment, and analysis
Two reviewers independently extracted data and performed risk of bias assessment using an Excel-based form.Disagreements between individual judgements were resolved by a third reviewer.When multiple articles reported on the same study, data was combined into a single data extraction.
We extracted data on study characteristics-study location, sample size, eligible participants, sample collection process, including location and timing, anatomical site, specimen type, and sampling device, sample transport, stage medium, type of test, test threshold, and the number of GBS colonisation true positives (TP), false positives (FP), true negatives (TN), and false negatives (FN).
Our review outcomes (see Additional file 3) were diagnostic accuracy, and maternal, perinatal and neonatal outcomes.Additional secondary outcomes were outcome of sampling order, uptake of self-collection, case finding, linkage of positive test to clinical assessment or treatment, feasibility, and patient acceptability and preference.Missing or unclear information was noted as such.Where review outcome data were missing, we contacted study investigators to see if additional data were available.Risk of bias in the included studies and concerns regarding applicability to the review question were assessed independently by two reviewers using the QUADAS-2 checklist [25].Any disagreements were resolved by a third reviewer.
Meta-analysis was conducted according to the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy, Version 2.0 [26].Trials and non-trials were analysed separately.Revman 5.4 was used to generate forest plots for sensitivity and specificity.Other analyses were performed using Stata SE version 17 (STATA Corp., Texas, USA).Using the Stata command metandi, we calculated the sensitivity and specificity for each study and pooled these estimates using a bivariate, randomeffects, meta-analytic model.This model is required to describe variability in accuracy between studies, due to expected heterogeneity [26].A Hierarchical Summary Receiver Operating Characteristic (HSROC) plot was constructed using metandi, which provides a global summary of both sensitivity and specificity estimates and accounts for between-study variability [27].The HSROC plot presented sensitivity and specificity estimates from individual studies, the pooled estimates, 95% confidence interval (CI), and 95% prediction interval, i.e. the confidence region for a forecast of true sensitivity and specificity in a future study [27].
Since no covariates were included in the meta-analysis, the bivariate and HSROC models were mathematically equivalent [28] and thus presented together.Stata's metadta command was used to calculate the bivariate I 2 value, which measures heterogeneity whilst accounting for the correlation between logit sensitivity and logit specificity [29].Meta-regression was not done because there were less than ten studies in each meta-analysis [26].There were insufficient or zero studies to undertake subgroup analyses by sample anatomical site, gestational age (GA), culture technique, or NAAT thresholds.Forest plots were instead examined visually for any trends in pre-specified subgroups of interest.
Sensitivity analyses were conducted to investigate the effect of non-randomised studies on the summary estimates which (1) included participants at < 35 weeks' gestation (n = 3) and (2) did not incubate all culture samples in enriched culture media (n = 1).There were too few studies for further sensitivity analyses.

Screening results
The search identified 5909 citations (Fig. 1).A total of 3913 citations were excluded following title/abstract screening.Nine further articles were retrieved from manual searching of reference lists.On full text review, 223 citations were excluded, with reasons outlined in Fig. 1 and Additional file 4, leaving 30 articles reporting on 5 RTIs.
No included studies which compared self-collected and provider-collected samples taken from different participants measured the outcome of maternal, perinatal, and/or neonatal outcomes, allowing comparison of risk of health outcomes between self-collection and provider-collection.
The delay between self-sampling and provider sampling was short, with all self-collected and provider-collected swabs taken on the same day, except for one study [32], where samples may have been taken at different visits.In the four randomised cross-over trials [19,31,36,39], participants were randomised to two groups, determining the order in which self-collected and provider-collected swabs were taken, with the comparative group's swabs taken in the reverse order.One study [37] employed a similar cross-over design with participants split into two groups, but participant allocation was not randomised.
The overall methodological quality of the included studies was generally poor (Table 2, Additional file 6 [17,19,20,[31][32][33][34][35][36][37][38][39]).No studies were at low risk of bias for all domains, though several studies did not report sufficient detail for some domains.There were no concerns regarding applicability, i.e. the extent to which included studies answered the review question.
On visual inspection of forest plots (Fig. 3) to compare studies that could have been part of subgroups, no obvious trends were observed.
In the randomised trials, heterogeneity for sensitivity (68.85%) was higher than that of specificity (12.08%), and for non-randomised studies, heterogeneity for specificity (72.50%) was higher than that of sensitivity  (37.38%) (Table 4).Despite the high I 2 for sensitivity and specificity, the generalised between-study I 2 was close to zero, which can be attributed to the correlation between sensitivity and specificity (rho = − 1.00 and − 0.51) [40].Sensitivity analyses are detailed in Additional file 7 [20,33,34,37,38].

Key findings
This review sought to determine whether self-collected samples are as accurate as provider-collected samples for the same test for detection of GBS colonisation in pregnant individuals.We found a limited evidence base (11 studies), there were possible integrity concerns for three trials, and no study was assessed as low risk of bias overall.Hence, it is possible that further high-quality research may draw different conclusions.We pooled eleven studies Fig. 2 HSROC plots of randomised (left) and non-randomised (right) GBS studies that compared self-collection to provider-collection: The circles represent individual study estimates, with circle size proportional to sample size of each study.The continuous green line is the summary curve from the model.The red square represents the summary estimate for sensitivity and specificity and the yellow dotted line represents the 95% confidence region for this summary estimate.The green dotted line represents the 95% prediction region Fig. 3 Forest plots of randomised (top) and non-randomised (bottom) studies that compare self-collected samples to provider-collected samples for GBS testing (3269 paired samples) and found generally high accuracy of self-collected compared to provider-collected samples for GBS detection.No study reported on whether a strategy of self-collection compared to provider-collection has an effect on maternal and perinatal health outcomes.
Meta-analysis of eleven studies found sensitivities of 82% (95% CI: 66-91%) and 91% (95% CI: 83-96%) and specificities of 99% (95% CI: 98-99%) and 97% (95% CI: 94-99%) for self-collection of samples for GBS testing in randomised trials and non-randomised studies, respectively.Individual point estimates were similar, with overlapping 95% CIs for sensitivity and specificity in most studies.The overall high sensitivity and specificity of selfcollected swabs compared to provider-collected swabs supports the use of self-collection of samples for detection of GBS colonisation.However, among the eleven studies included in our analysis, particularly the four trials, the overall results indicate acceptable specificity, but lower sensitivity, with a wide 95% CI for the sensitivity summary estimate for trials (66-91%).
In ten studies [17,19,20,[31][32][33][35][36][37][38][39], self-collection occurred in the clinic.In the one study [34] in which selfcollection occurred at home, 3 to 7 weeks after receiving instructions, 27.3% (n = 52/190) of participants reported difficulties with self-collection.In that study, providercollection occurred on the same day as self-collection after participants brought their self-collected samples to the clinic.However, the sensitivity and specificity point estimates were still high-Se 97% (95% CI: 82-100%), Sp 99% (95% CI: 96-100%).A self-sampling strategy will allow individuals to collect their own samples at a convenient time and location.Whilst the results from this study using self-collection outside of the clinic setting are promising, further confirmatory studies are needed.
In one study [36], the majority of participants (66.6%, n = 273/410) reported difficulty with self-collection, despite written information sheets and a short instructional video.This study had the lowest sensitivity point estimate of the included studies (Se 60% [95% CI: 49-71%], Sp 99% [98% CI: 96-100%]).Whilst all studies provided information to participants on self-collection procedures, this information was not standardised nor assessed for participant understanding-this is a potential source of variation in accuracy of self-collection.There may be a role for guidelines that provide standardised self-collection instructions and processes.In the studies that reported on self-collection uptake, a proportion of eligible participants declined the option, and in the studies that reported on sampling preference, there was even split between those favouring provider-collection or self-collection.This highlights the importance of allowing availability of options, including self-care interventions, to expand patient choice and autonomy.

Strengths and limitations
To our knowledge, this is the first systematic review on self-collection of samples for RTI testing, including GBS, in pregnant individuals.Strengths of this review involved searching a large number of databases without language or publication date limitations, and sourcing additional outcome data through contacting study investigators.We embedded a novel adapted RIA tool, which identified that some of the included trials could be problematic.We did not exclude these trials on this basis alone, requested further data from triallists, and reported all RIA domains for transparency.All included studies made direct within-study comparisons, by performing the same test on self-collected and provider-collected samples from all participants.Hence, each participant acted as their own control and studies were thus less prone to bias due to confounding [26].This review nonetheless has some limitations.One possible limitation is that we may not have identified studies of primarily non-pregnant patients that may have included a subpopulation of pregnant individuals.To mitigate this, we sought support from a librarian for our search strategy, and we screened full texts for any mention of pregnancy, even when the title or abstract did not suggest it.

Implications for policy, clinical practice, and future research
Our findings support offering the choice of sample selfcollection for GBS detection in antenatal care settings, particularly given the high sensitivity and specificity of self-collected compared to provider-collected samples, and the finding that many people accept (and even prefer) this approach.However, given the limited evidence base, with all studies at high or unclear risk of bias, caution must be taken when interpreting the meta-analysis findings of sensitivity and specificity.No studies were found on the effect of self-collection on maternal, perinatal, or neonatal health outcomes, so we could not explore whether this strategy is better or worse in terms of pregnancy-related outcomes.WHO guidelines note that large multicentre trials are needed to evaluate the effects GBS screening and confirm whether screening reduces preterm birth and perinatal mortality in low-and middleincome countries [41].

Conclusions
Expanding GBS screening and task-shifting away from clinical services to home-based and community service testing could expand access and decrease burden on healthcare systems.This is particularly so in limitedresource settings with healthcare infrastructure limitations, although sample processing is dependent on the availability of laboratory services and trained staff, which may not be feasible in all low-income country settings.
Nearly all studies we identified were conducted in highincome countries; self-collection could be useful for individuals in rural and remote regions in high-income countries if the option of posting samples was available.The evidence from this meta-analysis supports the option of self-collection of samples for GBS testing for individuals who decline provider-collection, who are hard to reach, or face barriers to antenatal care.Availability of accurate sampling options for screening to suit patient choice can hopefully improve uptake of GBS testing and thus reduce the incidence of EOGBS.In high-income settings with universal GBS screening in pregnancy, prevalence of adherence to antenatal GBS screening has been reported as ranging from 52 to 85.5% in Australian and US studies [42][43][44].
Whilst sample self-collection, as an additional option to provider-collection for detection of GBS colonisation, is promising, further research is required to determine whether self-collection at home, without same-day instructions on how to self-collect, would be as accurate, and improve uptake.

Fig. 1
Fig.1PRISMA flowchart[30] of identification and selection of studies

Table 1
Key characteristics of included studies

Table 2
Risk of bias assessment of the included studies

Table 3
Pooled sensitivity and specificity from randomised (left) and non-randomised (right) studies that compared self-collected to provider-collected samples for GBS testing

Table 4
Between-study heterogeneity statistics for randomised (left) and non-randomised (right) GBS studies that compare selfcollection to provider-collection